Red yeast rice is what is referred to as a “koji” in Japanese, meaning “grain or bean overgrown with a mold culture”, a food preparation tradition going back to ca. 300 BC. In both the scientific and popular literature in English that draws principally on Japanese, red yeast rice is most often referred to as “red rice koji“.[1] English language articles favoring Chinese literature sources prefer the translation “red yeast rice.”

Contents

Production

Red yeast rice is produced by cultivating the yeast species Monascus purpureus on rice. The rice is first soaked in water until the grains are fully saturated. The raw soaked rice can then either be directly inoculated or it can be steamed for the purpose of sterilizing and cooking the grains prior to inoculation. Inoculation is done by mixing either M. purpureus spores or powdered red yeast rice together with the rice that is being treated. The mix is then incubated in an environment around room temperature for 3–6 days. During this period of time, the rice should be fully cultured with M. purpureus, with each rice grain turning bright red in its core and reddish purple on the outside.[2] The fully cultured rice is then either sold as the dried grain, or cooked and pasteurized to be sold as a wet paste, or dried and pulverized to be sold as a fine powder. China is the world’s largest producer of red yeast rice, but European companies have entered the market.[3]

Uses

Culinary

Red yeast rice is used to color a wide variety of food products, including pickled tofu, red rice vinegar, char siu, Peking Duck, and Chinese pastries that require red food coloring. It is also traditionally used in the production of several types of Chinese huangjiu (Shaoxing jiu), and Japanese sake (akaisake), imparting a reddish color to these wines.[4] Although used mainly for its color in cuisine, red yeast rice imparts a subtle but pleasant taste to food and is commonly used in the cuisine of the Fujian province of China.[5] Red yeast rice (angkak in Filipino) is also used widely in the Philippines to traditionally color and preserve certain dishes like fermented shrimp (bagoong alamang), burong isda (fermented rice and fish), and balao-balao (fermented rice and shrimp).[6][7][8]

Traditional Chinese medicine

In addition to its culinary use, red yeast rice is also used in Chinese herbology and traditional Chinese medicine. Its use has been documented as far back as the Tang Dynasty in China in 800 AD. It is taken internally to invigorate the body, aid in digestion, and revitalize the blood.[9] A more complete description is in the traditional Chinese pharmacopoeia, Ben Cao Gang Mu-Dan Shi Bu Yi, from the Ming Dynasty (1378–1644).[10]

Red yeast rice and ‘statin’ drugs

In the late 1970s, researchers in the United States and Japan were isolating lovastatin from Aspergillus and monacolins from Monascus, respectively, the latter being the same fungus used to make red yeast rice but cultured under carefully controlled conditions. Chemical analysis soon showed that lovastatin and monacolin K are identical. The article “The origin of statins” summarizes how the two isolations, documentations and patent applications were just months apart.[11] Lovastatin became the patented, prescription drug Mevacor.[12] Red yeast rice went on to become a contentious, non-prescription dietary supplement in the United States and other countries.

Lovastatin and other prescription ‘statin‘ drugs inhibit cholesterol synthesis by blocking action of the enzyme HMG-CoA reductase. As a consequence, circulating total cholesterol and LDL-cholesterol are lowered by 24-49% depending on the statin and dose.[13] Different strains of Monascus fungus will produce different amounts of monacolins. The ‘Went’ strain of Monascus purpureus (purpureus = dark red in Latin), when properly fermented and processed, will yield a dried red yeast rice powder that is approximately 0.4% monacolins, of which roughly half will be monacolin K (identical to lovastatin). Monacolin content of a red yeast rice product is described in a 2008 clinical trial report.[14]

Regulatory restrictions

The US Food and Drug Administration (FDA) position is that red yeast rice products that contain monacolin K, i.e., lovastatin, are identical to a drug and, thus, subject to regulation as a drug. In 1998, the FDA initiated action to ban a product (Cholestin) containing red yeast rice extract. The U.S. District Court in Utah allowed the product to be sold without restriction. This decision was reversed on appeal to the U.S. Court of Appeals. (Moore, 2001) (see External links: PDRhealth). Thereafter, the FDA sent Warning Letters to companies selling red yeast rice. The product disappeared from the market for a few years.

In 2003, red yeast rice products began to reappear in the U.S. market. In 2007, the FDA sent Warning Letters to two dietary supplement companies. One was making a monacolin content claim about its RYR product and the other was not, but the FDA noted that both products contained monacolins. Both products were withdrawn.[15] In this press release the FDA stated that consumers should “… not buy or eat red yeast rice products … may contain an unauthorized drug that could be harmful to health.” The rationale for “… harmful to health …” was that consumers might not understand that the dangers of monacolin-containing red yeast rice might be the same as those of prescription statin drugs.[15]

A products analysis report from 2010 tested 12 products commercially available in the US and reported that per 600 mg capsule, total monacolins content ranged from 0.31 to 11.15 mg.[16] A 2017 study tested 28 brands of red yeast rice supplements purchased from US retailers, stating “the quantity of monacolin K varied from none to prescription strength […]”[17] Many of these avoid FDA regulation by not having any appreciable monacolin content. Their labels and websites say no more than “fermented according to traditional Asian methods” or “similar to that used in culinary applications.” The labeling on these products often says nothing about cholesterol. If they do not contain lovastatin, do not claim to contain lovastatin, and do not make a claim to lower cholesterol, they are not subject to FDA action. Two reviews confirm that the monacolin content of red yeast rice dietary supplements can vary over a wide range, with some containing negligible monacolins.[18][19]

Clinical evidence

The amount typically used in clinical trials is 1200–2400 mg/day of red yeast rice containing approximately 10 mg total monacolins, of which half are monacolin K. This does raise a question about the function of the other monacolins and non-monacolin compounds in the products, as the monacolin K content is lower than what is usually considered effective for lovastatin (20–80 mg/day). A meta-analysis reported LDL-cholesterol lowered by 1.02 mmol/L (39.4 mg/dL) compared to placebo. The incidence of reported adverse effects ranged from 0% to 5% and was not different from controls.[20] A second meta-analysis incorporating more recent clinical trials reported significant lowering of total cholesterol and LDL-cholesterol.[21]

Within the first review,[20] the largest and longest duration trial was conducted in China: the China Coronary Secondary Prevention Study (CCSPS). Close to 5,000 post-heart attack patients were enrolled for an average of 4.5 years to receive either a placebo or a RYR product named Xuezhikang (血脂康). The test product was an ethanol extract of red yeast rice, with a monacolin K content of 11.6 mg/day. Key CCSPS results: In the treated group, risk of subsequent heart attacks was reduced by 45%, cardio deaths by 31%, and all-cause deaths by 33%.[22]

The CCSPS heart attack and cardiovascular death outcomes appear to be better than what has been reported for prescription statin drugs. A 2008 review pointed out that the cardioprotective effects of statins in Japanese populations occur at lower doses than are needed in Western populations, and theorized that the low amount of monacolins found in Xuezhikang might have been more effectively athero-protective than expected in the Chinese population in the CCSPS study for the same reason.[23]

Safety

The safety of red yeast rice products has not been established, and some commercial supplements have been found to contain high levels of the toxincitrinin.[16] As commercial products will have highly variable amounts of monacolins,[16] and rarely declare this content on the label, defining risk is difficult. Ingredient suppliers have also been suspected of “spiking” red yeast rice preparations with purified lovastatin. As evidence, one published analysis reported several commercial products as being almost entirely monacolin K – which would occur if the drug lovastatin was added – rather than the expected composition of many monacolin compounds.[18] Statin drugs are known to cause muscle and liver damage. Statin-associated rhabdomyolysis can lead to kidney damage and possibly kidney failure (renal failure). This is why they are prescription drugs rather than over-the-counter, and with recommendations that the patients’ physicians schedule liver function tests on a regular basis. There are reports in the literature of muscle myopathy and liver damage resulting from red yeast rice usage.[24] From a placebo-controlled trial in patients with known statin-associated myalgias, in the treated group, two patients dropped out because of myalgia, 1 for diarrhea, and 1 for dizziness. In the placebo group, one dropped out for myalgia. Creatine phosphokinase increased slightly in the treated group (from 122 to 128 IU/L) versus decreasing with placebo (117 to 101 IU/L), but the shifts were not statistically significant. Subjective muscle pain scores were similar for the two groups.[25] “The potential safety signals of myopathies and liver injury raise the hypothesis that the safety profile of RYR is similar to that of statins. Continuous monitoring of dietary supplements should be promoted to finally characterize their risk profile, thus supporting regulatory bodies for appropriate actions.”[26] The European Food Safety Authority (EFSA) Panel on Food Additives and Nutrient Sources added to Food concluded that when red yeast rice preparations contained monacolins, the Panel was unable to identify an intake that it could consider as safe. The reason given was case study reports of severe adverse reactions to products containing monacolins at amounts as low as 3 mg/day.[27]

Red yeast rice is not recommended during pregnancy or breast-feeding.[28]